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After attending lectures, reading the text and working assigned problems related to this chapter, students will have acquired the following knowledge and abilities: Know the origin of the unusual acidity of H α atoms located between two carbonyl groups, know the relative acidity of H α in aldehydes, ketones, esters, and 1,3-dicarbonyls; given starting material and reaction conditions, predict the major product that will form;. | Chapter 23: Ester Enolates and the Claisen Condensation Recall the aldol addition: Can we do this with ester enolates? The Claisen Condensation Driven by deprotonation of 3-oxoalkanoate (“β–ketoester”). Endothermic as written “Ketoester” versus two esters Mechanism: Addition-Elimination Has to be the same or transesterification will occur Acidic Claisen Products of Claisen condensation are alkyl 3-oxoalkanoates (IUPAC), common name β-keto-esters and, generally, β-dicarbonyl compounds The hydrogens between the two carbonyls are unusually acidic: Due to inductive effect of two carbonyls and resonance in the anion. Low pKas mean that alkoxide or hydroxide can make the enolates stoichiometrically! Acidity of Claisen product is essential to drive the reaction. Without the acidic H, reaction goes in the reverse! No go, starting on the left. Goes from right to left, when starting with the product (made by a different route, as will be seen later). Mechanism of reverse Claisen . | Chapter 23: Ester Enolates and the Claisen Condensation Recall the aldol addition: Can we do this with ester enolates? The Claisen Condensation Driven by deprotonation of 3-oxoalkanoate (“β–ketoester”). Endothermic as written “Ketoester” versus two esters Mechanism: Addition-Elimination Has to be the same or transesterification will occur Acidic Claisen Products of Claisen condensation are alkyl 3-oxoalkanoates (IUPAC), common name β-keto-esters and, generally, β-dicarbonyl compounds The hydrogens between the two carbonyls are unusually acidic: Due to inductive effect of two carbonyls and resonance in the anion. Low pKas mean that alkoxide or hydroxide can make the enolates stoichiometrically! Acidity of Claisen product is essential to drive the reaction. Without the acidic H, reaction goes in the reverse! No go, starting on the left. Goes from right to left, when starting with the product (made by a different route, as will be seen later). Mechanism of reverse Claisen condensation: But: If one partner has no α-hydrogens (not enolizable), then Crossed Claisen Condensation Gives mixtures of products (as in the case of the crossed aldol addition). To minimize selfcondensation of ethyl propanoate, the benzoate ester is used in excess. 11/16/2014 © Univesity of California 8 Mixed Ketone Claisen Condensation Ketones are more acidic than esters, function as enolate partners. Their competitive aldol additions are reversible, but Claisen is not. pKa = 19 pKa = 25 This is general for Intramolecular Claisen Condensation (Dieckmann Condensation) Ethyl 2-oxocyclohexanecarboxylate Mixed Claisen-Dieckmann Condensation Walter Dieckmann 1869-1925 Use of β-Dicarbonyl Compounds acidic Derived enolates are relatively non-basic, but good nucleophiles: Particularly useful for oxoesters, because they can be decarbonylated: Alkylation: Note: Rsec! Recall: Can’t make disubstituted system by direct Claisen condensation Enol Keto Decarboxylation: Acetoacetic ester synthesis makes .
